Silchenko AS et al. (2023), Djakonoviosides A, A1, A2, B1-B4 - Triterpene M...

ECB-ART-51297

Int J Mol Sci 2023 Jul 05;2413:. doi: 10.3390/ijms241311128.

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Djakonoviosides A, A1, A2, B1-B4 - Triterpene Monosulfated Tetra- and Pentaosides from the Sea Cucumber Cucumaria djakonovi: The First Finding of a Hemiketal Fragment in the Aglycones; Activity against Human Breast Cancer Cell Lines.

Silchenko AS , Kalinovsky AI , Avilov SA , Popov RS , Dmitrenok PS , Chingizova EA , Menchinskaya ES , Panina EG , Stepanov VG , Kalinin VI , Stonik VA .

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Seven new monosulfated triterpene glycosides, djakonoviosides A (1), A1 (2), A2 (3), and B1-B4 (4-7), along with three known glycosides found earlier in the other Cucumaria species, namely okhotoside A1-1, cucumarioside A0-1, and frondoside D, have been isolated from the far eastern sea cucumber Cucumaria djakonovi (Cucumariidae, Dendrochirotida). The structures were established on the basis of extensive analysis of 1D and 2D NMR spectra and confirmed by HR-ESI-MS data. The compounds of groups A and B differ from each other in their carbohydrate chains, namely monosulfated tetrasaccharide chains are inherent to group A and pentasaccharide chains with one sulfate group, branched by C-2 Qui2, are characteristic of group B. The aglycones of djakonoviosides A2 (3), B2 (5), and B4 (7) are characterized by a unique structural feature, a 23,16-hemiketal fragment found first in the sea cucumbers' glycosides. The biosynthetic pathway of its formation is discussed. The set of aglycones of C. djakonovi glycosides was species specific because of the presence of new aglycones. At the same time, the finding in C. djakonovi of the known glycosides isolated earlier from the other species of Cucumaria, as well as the set of carbohydrate chains characteristic of the glycosides of all investigated representatives of the genus Cucumaria, demonstrated the significance of these glycosides as chemotaxonomic markers. The membranolytic actions of compounds 1-7 and known glycosides okhotoside A1-1, cucumarioside A0-1, and frondoside D, isolated from C. djakonovi against human cell lines, including erythrocytes and breast cancer cells (MCF-7, T-47D, and triple negative MDA-MB-231), as well as leukemia HL-60 and the embryonic kidney HEK-293 cell line, have been studied. Okhotoside A1-1 was the most active compound from the series because of the presence of a tetrasaccharide linear chain and holostane aglycone with a 7(8)-double bond and 16β-O-acetoxy group, cucumarioside A0-1, having the same aglycone, was slightly less active because of the presence of branching xylose residue at C-2 Qui2. Generally, the activity of the djakonoviosides of group A was higher than that of the djakonoviosides of group B containing the same aglycones, indicating the significance of a linear chain containing four monosaccharide residues for the demonstration of membranolytic action by the glycosides. All the compounds containing hemiketal fragments, djakonovioside A2 (3), B2 (5), and B4 (7), were almost inactive. The most aggressive triple-negative MDA-MB-231 breast cancer cell line was the most sensitive to the glycosides action when compared with the other cancer cells. Okhotoside A1-1 and cucumarioside A0-1 demonstrated promising effects against MDA-MB-231 cells, significantly inhibiting the migration, as well as the formation and growth, of colonies.

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References [+] :

Aminin, Antitumor activity of the immunomodulatory lead Cumaside. 2010, Pubmed, Echinobase

Aminin, Antitumor activity of the immunomodulatory lead Cumaside. 2010, Pubmed , Echinobase
Dyshlovoy, Frondoside A induces AIF-associated caspase-independent apoptosis in Burkitt lymphoma cells. 2017, Pubmed
Dyshlovoy, The marine triterpene glycoside frondoside A induces p53-independent apoptosis and inhibits autophagy in urothelial carcinoma cells. 2017, Pubmed , Echinobase
Dyshlovoy, The marine triterpene glycoside frondoside A exhibits activity in vitro and in vivo in prostate cancer. 2016, Pubmed
Jin, Therapeutic effects of ginsenosides on breast cancer growth and metastasis. 2020, Pubmed
Kalinin, Triterpene glycosides of sea cucumbers (Holothuroidea, Echinodermata) as taxonomic markers. 2015, Pubmed , Echinobase
Kalinovsky, The Assignment of the Absolute Configuration of C-22 Chiral Center in the Aglycones of Triterpene Glycosides from the Sea Cucumber Cladolabes schmeltzi and Chemical Transformations of Cladoloside C. 2015, Pubmed , Echinobase
Mondol, Sea Cucumber Glycosides: Chemical Structures, Producing Species and Important Biological Properties. 2017, Pubmed , Echinobase
Park, Relationships between chemical structures and functions of triterpene glycosides isolated from sea cucumbers. 2014, Pubmed , Echinobase
Seco, Assignment of the absolute configuration of polyfunctional compounds by NMR using chiral derivatizing agents. 2012, Pubmed
Sil'chenko, [Monosulfated triterpene glycosides from Cucumaria okhotensis Levin et Stepanov, a new species of sea cucumbers from Sea of Okhotsk]. 2007, Pubmed , Echinobase
Silchenko, Structures and Biogenesis of Fallaxosides D₄, D₅, D₆ and D₇, Trisulfated Non-Holostane Triterpene Glycosides from the Sea Cucumber Cucumaria fallax. 2016, Pubmed , Echinobase
Silchenko, Constituents of the sea cucumber Cucumaria okhotensis. Structures of okhotosides B1-B3 and cytotoxic activities of some glycosides from this species. 2008, Pubmed , Echinobase
Silchenko, Kurilosides A1, A2, C1, D, E and F-Triterpene Glycosides from the Far Eastern Sea Cucumber Thyonidium (= Duasmodactyla) kurilensis (Levin): Structures with Unusual Non-Holostane Aglycones and Cytotoxicities. 2020, Pubmed , Echinobase
Silchenko, Chilensosides E, F, and G-New Tetrasulfated Triterpene Glycosides from the Sea Cucumber Paracaudina chilensis (Caudinidae, Molpadida): Structures, Activity, and Biogenesis. 2023, Pubmed , Echinobase
Silchenko, Structure of cucumariosides H5, H6, H7 and H8, triterpene glycosides from the sea cucumber Eupentacta fraudatrix and unprecedented aglycone with 16,22-epoxy-group. 2011, Pubmed , Echinobase
Silchenko, Structures and Biologic Activity of Chitonoidosides I, J, K, K1 and L-Triterpene Di-, Tri- and Tetrasulfated Hexaosides from the Sea Cucumber Psolus chitonoides. 2022, Pubmed , Echinobase
Silchenkoa, Fallaxosides C₁, C₂, D₁ and D₂, Unusual Oligosulfated Triterpene Glycosides from the Sea Cucumber Cucumariafallax (Cucumariidae, Dendrochirotida, Holothurioidea) and Taxonomic Status of this Animal. 2016, Pubmed , Echinobase
Yayli, A triterpenoid saponin from Cucumaria frondosa. 1999, Pubmed , Echinobase
Yun, Holotoxin A₁ Induces Apoptosis by Activating Acid Sphingomyelinase and Neutral Sphingomyelinase in K562 and Human Primary Leukemia Cells. 2018, Pubmed , Echinobase
Zelepuga, Structure-Activity Relationships of Holothuroid's Triterpene Glycosides and Some In Silico Insights Obtained by Molecular Dynamics Study on the Mechanisms of Their Membranolytic Action. 2021, Pubmed , Echinobase
Zhu, Inhibition of Growth and Metastasis of Colon Cancer by Delivering 5-Fluorouracil-loaded Pluronic P85 Copolymer Micelles. 2016, Pubmed

	Figure 1. Chemical structures of glycosides isolated from Cucumaria djakonovi: 1—djakonovioside A; 2—djakonovioside A1; 3—djakonovioside A2; 4—djakonovioside B1; 5—djakonovioside B2; 6—djakonovioside B3; and 7—djakonovioside B4.
	Figure 2. MM2-optimized models of the aglycone of djakonoviosides A2 (3) and B4 (7) with 23α-OH (A) and 23β-OH (B) and interatomic distances between H-22 and H2-24 in Å.
	Figure 3. Chemical structure of acetylated derivatives 7a and 7b of djakonovioside B4 (7).
	Figure 4. The scheme of biosynthesis of holostane and non-holostane aglycones of the glycosides of C. djakonovi.
	Figure 5. Cytotoxic effect of the glycosides: (A)—djakonovioside A (1) (EC50 5.89, 4.45, and 3.77 μM for 24, 48, and 72 h, respectively); (B)—djakonovioside A1 (2) (9.64, 7.33, and 6.25 μM for 24, 48, and 72 h, respectively), (C)—cucumarioside A0-1 (EC50 6.04, 2.45, and 2.19 μM for 24, 48, and 72 h, respectively), and (D)—okhotoside A1-1 (2.34, 2.05, and 1.73 μM for 24, 48, and 72 h, respectively) on breast cancer cells MDA-MB-231 for 24 h, 48 h, and 72 h. All experiments were carried out in triplicate. The data are presented as mean ± SEM.
	Figure 6. The number of MDA-MB-231 cell colonies under treatment with different concentrations of cucumarioside A0-1, okhotoside A1-1, and djakonoviosides A (1) and A1 (2). Image J 1.52 software was used to count the cell colonies. Data are presented as means ± SEM. * p value ≤ 0.05 considered significant.
	Figure 7. Migration of MDA-MB-231 cells into wound areas observed with an MIB-2-FL fluorescence microscope of ten-fold magnification: (A)—0, 8, and 24 h after treatment with different concentrations of djakonovioside A (1). Cell migration into wound areas processed by Image J 1.52 software: (B)—0, 8, and 24 h after treatment with 0.25, 0.5, 1.0, and 2.0 μM of djakonovioside A (1); (C)—0, 8, and 24 h after treatment with 0.1, 0.5, 1.0, and 2.0 μM of djakonovioside A1 (2); (D)—0, 8, and 24 h after treatment with 0.05, 0.1, 0.25, and 0.5 μM of cucumarioside A0-1; (E)—0, 8, and 24 h after treatment with 0.05, 0.1, 0.25, and 0.5 μM of okhotoside A1-1. Data are presented as means ± SEM. * p value ≤ 0.05 considered significant.